The human antigen R, called HuR, (Humans antigen R), encoded by the ELAVL1 gene, is a RNA binding protein (RBP, RNA binding protein) with an important role in various post-transcriptional events for thousands of coding and non-coding RNAs. HuR is one of the most important elements of trans (trans-acting factors) type which recognizes, with high affinity, AU rich sequences (AREs) and modulates the half-lives of target RNAs, their translatability, the splicing and their localization. In this way, indirectly, it modulates the protein synthesis.
In normal tissues, the HuR activity is critical to guarantee the cell survival, differentiation and proliferation. High HuR levels have been associated with aggressive breast, ovarian, urothelium, bladder, intestine and lung cancers, which show more serious progression and for which an accumulation of cytoplasmic HuR is correlated with an adverse prognosis for patients. The HuR deregulation has been also correlated with inflammatory diseases and tumor diseases, where a physiological alteration of its target RNAs has been observed.
Compounds supposed to be able to inhibit the interaction between HuR and mRNA have been prepared in the past, however they have not provided the desired results. Dihydrotanshinone, of the following formula:
is a natural product derived from Danshen (Salvia miltiorrhiza Bunge), widely used in Asia for the treatment of inflammatory diseases, which has been recently described as having anti-tumor activity. Its activity mechanism, however, has not been elucidated to date.